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Dogs that develop lymphoma feel well despite their enlarged lymph nodes. It surprises pet owners to learn that this disease may kill dogs within three weeks to three months if left untreated.
Dr. Villalobos recommends that canine lymphoma patients be treated with combination chemotherapy using Wisconsin based protocols that include L-asparaginase and adriamycin blended into the popular COP protocols.
Remember, all pets that are receiving chemotherapy for any type of cancer require CBC’s in order to monitor for drug-induced myelosuppression. Ideally the CBC should be taken before each treatment. If the WBC is too low (<3,500) and if the Neutrophil count is below 1,800 antibiotics may be needed and the dose of the chemotherapy may need to be reduced or postponed.
The doses and sequence of chemotherapy protocols for Lymphoma must be rearranged for individual dogs depending on the severity of disease and the status of organ function. If the dog has liver or kidney disease, organomegaly (abnormal enlargement of the viscera) or if the lymphoma involves the liver, caution is the key during the induction. The protocol must be changed to administer the drugs over a two to seven day period with intense supportive care in the hospital.
Induction week is often a happy week as most dogs feel great being on Prednisone at 30 mg/M2 PO every q24h(every 24 hours) for 7 days. This shrinks the nodes and stimulates their appetite. Some clinicians choose only Predinsone as treatment, but the client should be advised that this is only one bullet in the six-shooter for therapy and that the dog will not survive any longer that the initial prognosis. Some oncologists feel that the use of Prednisone may increase the dog’s liability to the drug and develop resistance to future therapy.
The induction on day one is with Vincristine, which is given i.v. at 0.7 mg/M2.
L-asparginase is also given on day one at 10,000 i.v./M2 I.M. after pre-treatment with Benadryl and Dexamethazone. A recent paper presented at the October VCS meeting reported fewer hospitalizations and side effects such as sepsis and enteritis for those lymphoma dogs that received trimethoprim-sulfa during their induction.
The Prednisone is reduced to 20 mg/M2 q24(every 24 hours) for the second week and then 10 mg/M2 daily for the third week and then stopped. We use the Predinsone again when Cytoxan is given orally in order to encourage water intake and discourage cytoxan related hemorrhagic cystitis. Cytoxan is given PO at 200 mg/M2 over two days on week two. Adriamycin, the famous vasosclerotic, AKA, “Red Death,” is given with great caution as an I.V. on week three. The dose of adriamycin varies with the estimated actual lean body mass at 30 mg/M2 for medium to larger dogs or at 20 mg/M2 for dogs that are around 20 pounds or less.
Remember, if the dog is fat, the true lean body weight should be used for the dose calculation. If the dog is sick, anemic or thin, a dose reduction is wise. If the dog has heart disease, Adriamycin may worsen the problem as it is notorious for causing cardiomyopathy in humans and dogs. Breeds such as Doberman Pinchers that are susceptible to cardiomyopathy may be a greater risk if Adriamycin is used.
It is always in the pet’s best interest to consult with an oncologist for advice and guidance when using chemotherapy protocols for cancer patients. Vincristine is given on week four, Cytoxan with Prednisone is given on week five, then the Adriamycin again on week six. We have the client return on week eight for vincristine and a maintenance consultation.
We prefer to keep canines with lymphoma on permanent maintenance protocols. The caregiver is consulted and given options with my preference toward monthly visits for a physical exam, CBC and Vincristine. Following each visit for Vincristine, we rotate oral Cytoxan at the above dose and Chlorambucil at 1.4 mg/kg PO divided over 12 hours for maintenance of dogs that are initially presented with their lymphoma clinical stage I, II or III.
It is fair to say that no two oncologists treat their patients exactly the same. There are many ways to help dogs with lymphoma live a long and happy quality life. One way is to anticipate the side effects and send home a “care package” that treats nausea and vomiting. We often like to send Metaclopamide for nausea, anorexia and vomiting and Sulfasalizine for colitis.
The most important consideration in our practice is that we avoid distressing side effects and support the bond that brings the caregiver to us in the first place.
Resistance to the standard chemotherapy protocols causes heartbreak worldwide. Why cancer cells are able to resist the drugs we send into the host’s body to kill them is not such a mystery today as it was 20 years ago. The cancer cell is able to genetically code its genes to make little protein pumps on the cell surface membrane. These little pumps literally expel our drugs out of the cell. These molecular pumps are called MDR’s for their famous role in multiple drug resistance. Now it is important to know that their function is a survival mechanism for the body to detoxify itself. Treatments aimed at stopping this natural process without hurting the patient is illusive and would constitute a medical achievement. MDR’s are now recognized by certain research analysis and are being studied for targeted therapy in the future.
For now, we can only give drugs such as calcium channel blockers (verapamil) that may offset the action of the pumps. This may help win more time for our cancer patients that develop resistance to their chemotherapy.
In the meantime, most veterinarians adopt the first line of defense for dogs when they come out of remission with recurrent lymphoma. That first line is simply to reinstitute the induction protocol.
By repeating induction again with combination chemotherapy we hope for another remission. Most dogs will go back into complete remission on cycle #2. Unfortunately, the second remission is usually only half as long as the first remission and the third remission is half as long as the second and so on.
For resistant lymphoma and relapsed lymphoma, we try the switch and bait technique to see if we can trick the resistant tumor cells and see if we can win back another remission.
Vinblastine at 2 mg/M2 may have some effectiveness over Vincristine. Mitoxantrone may be effective where Adriamycin is not and DTIC may help where Cytoxan has failed.
For cutaneous lymphoma and resistant lymphoma, Lomustine at 50-85 mg/M2 divided over 4 days every 21 days is my preferred choice after a short reinduction. Since Lomustine causes significant myelosuppression after 3 to 4 cycles, increasing the interval between treatments to 5 to 8 weeks apart is generally recommended. This drug has been the most exciting addition to the few drugs that can claim a known efficiency against resistant lymphoid tumors. If this treatment is ineffective, it is recommended to review the entire history and drug sequence and identify which drug the pet was on when remission was lost. These drugs are then on my low priority list for using again. If it is determined that the relapsed lymphoma patient is resistant to previous chemotherapy, the use of the MOPP protocol can be expected to stabilize a majority.
MOPP provides 30% complete remission for about two months and some cases will go on to have a durable remission. The MOPP protocol involves more risk of G.I. side effects and sepsis, however, prophylactic antibiotic therapy may offset hospitalization. MOPP is: Mechlorethamine (Mustargen®) 3mg/M2 i.v. on day 1 and 8, Vincrisitne 0.7 mg/M2 i.v. on day 1 and 8, Procarbazine (Matulane®) 50mg/M2 PO and once daily for two weeks and Prednisone 30-40 mg/M2 PO daily for two weeks.
Remember that senior dogs diagnosed with cancer often have chronic pain. Butorphanol helps in these situations as an analgesic, antitussive, and anti-emetic. Piroxicam is well tolerated as an analgesic, and is my first choice due to its poorly understood antitumor effects. Caution should be taken always in oncology protocols that use steroids concomitantly. Fentanyl patches deliver a narcotic analgesic for 72 hours. Subcutaneous nalbuphine hydrochloride (Nubain®) can be administered at 0.5-1 mg/kg q3-4h (every 3-4 hours) it does not act like the typical sedation effects of most narcotic agents. It is not listed as a controlled substance and may be sent home with instructions for the caregivers to use as needed.
Owners like to pay special attention on their dog’s diet too, as they believe their senior dog can survive cancer even better with well-focused nutrition. Research institutions are also publishing data that shows that natural and synthetic substances can inhibit cancer via inhibition of mutagenesis, metastases, angiogenesis, and invasiveness. The role of a new set of cancer cell products called metalloproteinase inhibitors has researchers very interested. These MMP’s act to dissolve the membranes of cells and vessel walls allowing cancer cells to proceed with metastases. The October VCS meeting had many papers addressing the fundamental action and application of these products in cancer care.
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